genetics

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You might think the link between genes and weight is simple: Fat tends to run in families, right? But as researchers tease apart the underlying genetics of body weight, it becomes ever clearer that it is a complex trait. Very complex, with ultimately perhaps hundreds of genes involved in what you see when you step on the scale.

Today, the biggest-ever study of the genetics of obesity, involving genetic samples from nearly 350,000 people, reveals dozens of new spots on the human genome that are involved with body weight and body shape, according to two papers (here and here) published in the journal Nature.

My dominant impression: The data tend to implicate the brain as a powerful influence on overall body weight, but point more towards hormones and the fat cells themselves as strong determinants of whether we’re shaped like “apples” — with more upper body fat — or “pears,” with more fat concentrated below the waist.

Dr. Joel Hirschhorn, of Boston Children’s Hospital, the Broad Institute and Harvard Medical School, leads the Genetic Investigation of Anthropometric Traits consortium, or GIANT, the friendly collaborative of hundreds of researchers around the world who contributed to the studies. Our conversation, lightly edited:

How would you sum up the findings that come out in “Nature” today?

We did a very large genetic study looking at two different kinds of obesity: Overall obesity measured by body mass index and central obesity — fat around the belly — measured by waist circumference and hip circumference. And what we found was that there are a lot of genes that influence both types of obesity, but, really interestingly, the types of genes that influence overall obesity are actually quite different than the types of genes that influence where the fat goes on the body.

Interesting. So what does that tell us?

That tells us that even though both types of obesity are bad for your health, that it may be very important to understand what kind of obesity you have, because if the biology is different, that means the way we can treat that obesity, or prevent it effectively, is probably going to be different for the two kinds of obesity.

So it may matter even more than we thought whether you’re shaped like an ‘apple or a ‘pear’?

That’s right. It matters both whether you’re an apple or a pear and it matters just how big you are in general. But the way you get to be big in general is probably different than the way you get to be an apple or a pear.

So it’s different pathways? Perhaps whole different mechanisms at work?

That’s right. The overall obesity seems to have more to do with what’s going on in the brain, maybe controlling appetite or whether you get full or how quickly you get full. And the apple vs. pear seems to have more to do with your fat cells and hormones that your body makes, things like insulin.

So does all this translate into any action points for the general public?Continue reading →

Today on Radio Boston: A new Brigham and Women’s Hospital study finds that we may not need quite as much genetic counseling as we’d thought. Particularly on relatively cut-and-dried findings, like test results on a common gene that raises the risk of Alzheimer’s disease. Listen to host Anthony Brooks speak with Dr. Robert C. Green in the segment above.

From the Brigham’s press release:

A new study led by researchers at Brigham and Women’s Hospital (BWH) has found that people who received a written brochure instead of time-intensive genetic counseling about their genetic risk for Alzheimer’s disease did not experience greater anxiety or symptoms of depression than their counterparts a year later. The results of the randomized controlled study were published online in the journal Alzheimer’s and Dementia.

“As genetic testing of all kinds becomes commonplace, one of the primary challenges will be determining how to share this information with individuals seeking it in a way that limits the burden on health care providers but still puts the well-being of patients first,” said Robert C. Green, MD, MPH, a medical geneticist and researcher at BWH and Harvard Medical School and lead investigator of the study. “These new results show that for individuals seeking genetic risk information, we can use written material, rather than genetic counseling, to prepare them without causing greater long-term anxiety or distress.” Continue reading →

For years, futurists have foreseen an era when all newborn American babies would be sent home with a supply of self-knowledge: a readout of their full set of genes, with all it may imply about heightened chances for disease or health.

So how would you feel about that, as a new parent? Eager to absorb any possible indicator of your child’s potential future? Or wary that genes are not destiny, and you may spend a lifetime fearing something that never comes to pass?

“Several other studies have measured parents’ interest in newborn genomic screening, but none focused on new parents in the first 48 hours,” said Robert C. Green, MD, MPH, a geneticist and researcher at BWH and Harvard Medical School and senior author of the study. “Since this is when genomic testing would be of the greatest value, it is especially important to study parents’ attitudes immediately post-partum.”

The researchers surveyed 514 parents at the well baby nursery at BWH within 48 hours of their child’s birth. After receiving a brief orientation to the genome and its impacts on human health, including information about what the genome is, what genes are and how they can affect both health and medical care, 82.7 percent of parents reported being somewhat (36 percent), very, (28 percent) or extremely (18 percent) interested in newborn genomic testing. Results were similar regardless of parents’ age, gender, race, ethnicity, level of education, family history of genetic disease, or whether or not the infant was a first-born child. Parents who had experienced concerns about the health of their newborn, however, were less likely to be interested in genomic testing. Continue reading →

Every once in a while, I’m grateful I live in such a medically-minded town, with many deep thinkers trying to figure out treatments and cures for some very tough diseases.

I felt this way over the summer, at a conference in Boston on Facioscapulohumeral Muscular Dystrophy, a genetic disorder that affects 1 in 8,333 people and has no treatment. I did not attend the meeting due to some theoretical interest in the topic; for me, it’s personal.

My mother and grandmother suffered from the condition, and so does my brother. It causes gradual loss of muscle function, notably in the face, and in the muscles that mobilize the shoulder blades and the upper arm, but also in the legs.

My brother first developed symptoms when he was 15, and found that he could no longer run as fast as his high school soccer teammates. Since the age of 43, he has been confined to a wheelchair or scooter, unable to walk or stand.

But at the conference in August, I also realized that this illness with such a profound impact on my family, also has a global reach. Indeed, in regions like Africa, the condition is only just beginning to be acknowledged.

Enter: Chris Chege

I first saw Chege sitting on a tall stool at the back of the room with his wife. Their presence proved that the condition affects Africans, too, something that isn’t widely acknowledged. Chege and his wife had traveled to Boston from their home in Thika, in central Kenya, 30 miles Northeast of Nairobi.

An interview with Chege pointed to one possible reason that conference room was full, mainly, of white people: most people with the condition in Africa may not have been diagnosed with it yet.

But Chege said he sees others with FSHD in Kenya. He said he can tell.”By the way they walk,” he said. “I see them on national television when journalists go to their homes to interview them.” Continue reading →

Scientists say new “gene drive” technology could help fight malaria by affecting the mosquitoes that carry it. (Wikimedia Commons)

Perhaps you’ve followed that teeny tiny controversy around genetically modified foods, the “GMO” debate. Or you watched the fierce back-and-forth over whether it was a good idea to modify a strain of avian flu in the lab to make it spread more easily, in order to study it.

If this is your kind of spectator sport, it’s time to learn about gene drives, a powerful new genetic technology that basically flips Charles Darwin on his head, allowing a sort of artificial selection to help chosen genes come to dominate in a population.

I can already imagine the “pro” side of the debate: “This could eradicate malaria. Reduce the use of pesticides. Bolster agriculture for a crowded planet.” And the “con” side: “But what if it goes wrong out in the wild? Have you read no science fiction?”

I spoke with two of the paper’s co-authors: Kevin Esvelt, a technology development fellow at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School, who is also the lead author of the eLife paper; and Kenneth Oye, Professor in Engineering Systems and Political Science at MIT and director of policy and practices of the National Science Foundation’s Synthetic Biology Engineering Research Center. Our conversation, edited:

CG: So what exactly is a gene drive and why are we talking about it now?

Kevin Esvelt: A gene drive is a potential new technology that may let us alter the traits of wild populations but only over many generations. We think that gene drives have the potential to fix a lot of the problems that we’re currently facing, and that natural ecosystems are facing, because it allows us to alter wild populations in a way that we could never do before.

We would really like to start a public conversation about how we can develop it and use it responsibly, because we all depend on healthy ecosystems and share a responsibility to pass them on to future generations.

So how do they work? The reason we haven’t been able to alter wild populations to date is natural selection. When you say natural selection, you think, ‘How many organisms survive and reproduce?’ And that’s pretty much how it works. The more likely you are to survive and reproduce, then the more copies of your genes there are going to be. So genes that help an organism reproduce more often are going to be favored.

The problem is, when we want to alter a species, the way we want to alter it usually doesn’t help it survive and reproduce in nature. But that’s not the only way that a gene can reproduce. We have two copies of each gene, and when organisms have children, each of the offspring has a 50% chance of getting either copy. But you can imagine that a gene could gain an advantage if it could stack the deck — if it could ensure that it, rather than the alternate version, was inherited 70%, 80%, 90%, or 99% of the time.

How gene drives affect which genes are passed down (Courtesy Kevin Esvelt)

There are a lot of genes in nature that do exactly this; they’ve figured out an incredible variety of ways of doing that. Almost every species in nature has what we would call an ‘inheritance-biasing gene drive’ somewhere in its genome, or at the very least the broken remnants of one. They’re actually all over the place in nature.

The idea that we could harness these to spread our alterations through populations has actually been around for a long time. Continue reading →

February 25, 2014 | 1:37 PM | Karen Weintraub

FDA hearings in Washington this week have raised an ethical quandary: If we have the scientific power to help a sick woman give birth to healthy children, should we do it? Even if it requires us to cross an ethical line in the sand drawn decades ago by hundreds of nations worldwide?

A reproductive biologist from the Oregon Health and Science University in Beaverton, Shoukhrat Mitalipov, has asked the federal government for permission to test an unprecedented gene replacement technique in people. If he succeeds, women with mitochondrial diseases will be able to have their own, biological children, without passing on their disease.

But some others worry that this research will open up an ethical Pandora’s Box, legitimizing human genome manipulation. Plus, they say, the science is premature. This technique has only been tested in a handful of monkeys and it’s way too early to try in people, they say.

At root is some pretty technical science in an area that’s not yet well understood.
Mitochondrial disease is driven by mistakes in the 37 genes that drive the mitochondria — which, as you might remember from freshman biology, provide every cell with energy. Mitochondria is passed down from mother to child; the father’s mitochondria dies with him.

Mitalipov wants to get rid of the mother’s flawed mitochondria and replace them with a healthy donor’s. He would take the nucleus of an egg cell from the sick woman and implant it in an egg cell from a healthy donor, after the donor’s nucleus has been removed. When the egg is fertilized, the 20,000 genes in the mother’s nuclear genome will mix with the same number from the father’s, plus 37 healthy genes from the mitochondria of the donor. The result, Mitalipov says, will be a normal child.

Not everyone agrees with that last point. Even if the child appears healthy, it’s possible that it will have genetic problems during development, later in life or that will only appear when that child has children.

Sharon and Alana Aaarinen/Photo: Karen Weintraub

One potential problem: some of the mother’s unhealthy mitochondria will survive the transfer and show up in the child, unnoticed perhaps for generations, before another descendent gets sick. Mitalipov says this is impossible, that his technique promises nearly 100 percent swap of mitochondria, but some scientists remain unconvinced.

Mixing mitochondria from two “mothers” can put mice at higher risk for diabetes, stroke and heart disease, according to research.

Don’t miss this fascinating story by CommonHealth contributor Karen Weintraub detailing an ethically questionable new fertility treatment that involves three biological parents in order to avoid a rare but devastating mitochondrial disease.

Here’s the top of the piece, published in today’s New York Times:

Alana Saarinen sat at the piano, playing smoothly and with feeling. Behind her, plastic toys shared floor space with a book of plays she’d been writing. Her mother beamed.

Alana is apparently a normal, well-adjusted 13-year-old. But there is something extraordinary about her — every cell in her body is different in a way that is nearly unprecedented.

Alana was conceived with genetic material from three parents: Sharon and Paul Saarinen, who provided the egg and sperm, and a second woman who contributed genes to Alana’s mitochondria, the tiny power plants that fuel every cell.

The experimental technique making this possible — a cytoplasmic transfer, in Alana’s case — was halted by the Food and Drug Administration in 2001. Now, despite uncertainties about its safety, scientists in the United States and the United Kingdom are urging legalization of a more targeted version. Critics say it hasn’t been adequately studied and crosses the line into genetic engineering.

The story also explores the origins of the experimental cytoplasmic transfer and explains how the technique is being improved. Karen adds this in an email:

Researchers never followed the children born in the late 1990s and 2000s of this cytoplasm transfer technique, so it’s not clear what the risks are of this form of conception. Continue reading →

October 24, 2013 | 11:23 AM |

Don’t miss Lynn Jolicoeur’s excellent piece on WBUR this morning about the genetics of autism and the two young Natick boys, Tommy and Stuart Supple, whose gene mutations are the focus of research by Stanford neuroscientist Dr. Thomas Sudhof.

(Jesse Costa/WBUR)

From Lynn’s story:

…The Stanford University neuroscientist — who this year shared the Nobel Prize in medicine for his decades of study into how brain cells communicate — has been studying Tommy and Stuart’s genes, specifically an alteration in one gene, for five years. The Supples hosted Sudhof Wednesday night at a Boston fundraiser in support of his research into the functioning of brain synapses in autism…

According to the Supples, Sudhof’s work is helping conquer the “defeatism” surrounding the neurocognitive disorder.

“He doesn’t think this is unknowable at all. He thinks that it’s very knowable,” Kate Supple said. “We all put so much time and effort into dealing with the symptoms of autism. But you also have to look to deal with the underlying disease.”

For many parents of children with autism, the disorder is a mystery. They have no idea what caused it and focus on therapies to help address the symptoms. But after the blow of both boys being diagnosed before their 2nd birthdays, the Supples sought out private genetic testing without the encouragement of their doctors. Continue reading →

How would it change your life if you knew all your genes from the get-go? I mean, not just a little foray onto 23andMe when you’re 23 and curious, but a full sequencing of all your significant DNA at birth? Would you grow up with some deeply different ideas about yourself and your future than you would have otherwise? If, say, you knew you were at high risk for cancer or Alzheimer’s?

This is not just a thought experiment. Boston-based researchers have just announced that they will be seeking subjects for a $6-million study called BabySeq that involves sequencing more than 200 babies’ full sets of genes at birth, then following them to see how that genetic knowledge affects their lives and medical care. To which I say: Darn. This genomic future keeps arriving even faster than I expect.

The press release is below — Boston parents-to-be, take note: Recruitment is expected to begin early next year. I spoke with Dr. Robert C. Green, one of the lead researchers; our conversation, lightly edited:

So what is the question that this research project seeks to answer?

RCG: This is a research project at Brigham and Women’s Hospital and Boston Children’s Hospital, led by myself and Alan Beggs, that asks the question: What happens when you sequence newborn babies? What happens when you sequence healthy newborn babies and what happens when you sequence ill newborn babies?

The philopsophy with which we’ve started this project is that sequencing is here, it’s getting cheaper and cheaper, and more accessible. And everyone thinks that this is going to be a great boon to your health; it’s going to tell you about diseases and conditions that are going on, and it’s going to warn you about diseases and conditions to come. And we’d like to find out how this really plays out in these two very different situations.

If you have access to the reference book of life, and you can open it to any page you want, what do you get to read there, and how does it influence you?

In other words, if you have access to the reference book of life, and you can open it to any page you want, what do you get to read there, and how does it influence what your doctor does with you, what your doctor says to you, what your parent-and-child bonding is like? These are tremendously controversial issues, they’re issue we simply don’t know the answers to because the technology is so new, but it’s hurtling down the track at such speed that we must ask these questions as soon as we can, and as scientifically as we can, so that we understand the answers as the technology is being rolled out, not after it’s rolled out.

How many babies will be sequenced in this ‘BabySeq’ project?

There will be 480 babies enrolled, of whom half — or 240 — would be sequenced. It’s designed as a randomized, controlled trial. Continue reading →

If you’ve got $9,000 handy and a hankering to learn more about your genetic roadmap, here’s your chance.

Partners Healthcare, the largest hospital system in Massachusetts, announced yesterday that complete genomic sequencing is now available to patients. The full test would take 16 weeks, said spokesman Rich Copp, and insurance coverage would be determined on a case by case basis.

greyloch/flickr

Formerly a technique limited to the laboratory, complete genome sequencing maps the 3 billion pairs of DNA in a human’s genome. In recent years, scientific and technical advances have made genetic sequencing available for clinical use.

That’s a far cry from 2006, when scientists were still diagnosing a “market failure” in providing “rapid, low-cost medical grade genomes.” It was enough to spur the creation of the Archon Genomics X-Prize, which promised a $10 million prize to a team that could sequence 100 genomes in 30 days for less than $10,000 per genome. The X-Prize team ultimately called off the competition, citing commercial interests making the prize incentive superfluous:

What we realized is that genome sequencing technology is plummeting in cost and increasing in speed independent of our competition. Today, companies can do this for less than $5,000 per genome, in a few days or less – and are moving quickly towards the goals we set for the prize. – Peter Diamandis, chairman of X-Prize Committee

But where, exactly, will your new $9,000 map lead you? Shortly after he was diagnosed with cancer, Steve Jobs spent $100,000 on getting his genome completely sequenced. Continue reading →

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Massachusetts is the leading laboratory for health care reform in the nation, and a hub of medical innovation. From the lab to your doctor’s office, from the broad political stage to the numbers on your scale, we’d like CommonHealth to be your go-to source for news, conversation and smart analysis. Your hosts are Carey Goldberg, former Boston bureau chief of The New York Times, and Rachel Zimmerman, former health and medicine reporter for The Wall Street Journal.GET IN TOUCH

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Massachusetts is the leading laboratory for health care reform in the nation, and a hub of medical innovation. From the lab to your doctor’s office, from the broad political stage to the numbers on your scale, we’d like CommonHealth to be your go-to source for news, conversation and smart analysis. Your hosts are Carey Goldberg, former Boston bureau chief of The New York Times, and Rachel Zimmerman, former health and medicine reporter for The Wall Street Journal.

A new study on the growing problem of peanut allergy made a big splash this week. It’s no cure for kids who have it, but it does show how many children may avoid it. And it promises to accelerate the search for the cause of this mysterious epidemic.